Abstract

Thyrotoxicosis has multiple etiologies, manifestations, and potential therapies. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions and patient preference. This article describes evidence-based clinical guidelines for the management of thyrotoxicosis that would be useful to generalist and subspeciality physicians and others providing care for patients with this condition.The development of these guidelines was commissioned by the American Thyroid Association in association with the American Association of Clinical Endocrinologists. The American Thyroid Association and American Association of Clinical Endocrinologists assembled a task force of expert clinicians who authored this report. The task force examined relevant literature using a systematic PubMed search supplemented with additional published materials. An evidence-based medicine approach that incorporated the knowledge and experience of the panel was used to develop the text and a series of specific recommendations. The strength of the recommendations and the quality of evidence supporting each was rated according to the approach recommended by the Grading of Recommendations, Assessment, Development, and Evaluation Group.Clinical topics addressed include the initial evaluation and management of thyrotoxicosis; management of Graves' hyperthyroidism using radioactive iodine, antithyroid drugs, or surgery; management of toxic multinodular goiter or toxic adenoma using radioactive iodine or surgery; Graves' disease in children, adolescents, or pregnant patients; subclinical hyperthyroidism; hyperthyroidism in patients with Graves' ophthalmopathy; and management of other miscellaneous causes of thyrotoxicosis.One hundred evidence-based recommendations were developed to aid in the care of patients with thyrotoxicosis and to share what the task force believes is current, rational, and optimal medical practice.

Abstract

Thyrotoxicosis has multiple etiologies, manifestations, and potential therapies. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions and patient preference. This article describes evidence-based clinical guidelines for the management of thyrotoxicosis that would be useful to generalist and subspeciality physicians and others providing care for patients with this condition.The development of these guidelines was commissioned by the American Thyroid Association in association with the American Association of Clinical Endocrinologists. The American Thyroid Association and American Association of Clinical Endocrinologists assembled a task force of expert clinicians who authored this report. The task force examined relevant literature using a systematic PubMed search supplemented with additional published materials. An evidence-based medicine approach that incorporated the knowledge and experience of the panel was used to develop the text and a series of specific recommendations. The strength of the recommendations and the quality of evidence supporting each was rated according to the approach recommended by the Grading of Recommendations, Assessment, Development, and Evaluation Group.Clinical topics addressed include the initial evaluation and management of thyrotoxicosis; management of Graves' hyperthyroidism using radioactive iodine, antithyroid drugs, or surgery; management of toxic multinodular goiter or toxic adenoma using radioactive iodine or surgery; Graves' disease in children, adolescents, or pregnant patients; subclinical hyperthyroidism; hyperthyroidism in patients with Graves' ophthalmopathy; and management of other miscellaneous causes of thyrotoxicosis.One hundred evidence-based recommendations were developed to aid in the care of patients with thyrotoxicosis and to share what the task force believes is current, rational, and optimal medical practice.

Abstract

Radiation safety is an essential component in the treatment of patients with thyroid diseases by ¹³¹I. The American Thyroid Association created a task force to develop recommendations that would inform medical professionals about attainment of radiation safety for patients, family members, and the public. The task force was constituted so as to obtain advice, experience, and methods from relevant medical specialties and disciplines.Reviews of Nuclear Regulatory Commission regulations and International Commission on Radiological Protection [corrected] recommendations formed the basic structure of the recommendations. Members of the task force contributed both ideas and methods that are used at their respective institutions to aid groups responsible for treatments and that instruct patients and caregivers in the attainment of radiation safety. There are insufficient data on long-term outcomes to create evidence-based guidelines.The information was used to compile delineations of radiation safety. Factors and situations that govern implementation of safety practices are cited and discussed. Examples of the development of tables to ascertain the number of hours or days (24-hour cycles) of radiation precaution appropriate for individual patients treated with ¹³¹I for hyperthyroidism and thyroid cancer have been provided. Reminders in the form of a checklist are presented to assist in assessing patients while taking into account individual circumstances that would bear on radiation safety. Information is presented to supplement the treating physician's advice to patients and caregivers on precautions to be adopted within and outside the home.Recommendations, complying with Nuclear Regulatory Commission regulations and consistent with guidelines promulgated by the National Council on Radiation Protection and Measurement (NCRP-155), can help physicians and patients maintain radiation safety after treatment with ¹³¹I of patients with thyroid diseases. Both treating physicians and patients must be informed if radiation safety, an integral part of therapy with ¹³¹I, is to be attained. Based on current regulations and understanding of radiation exposures, recommendations have been made to guide physicians and patients in safe practices after treatment with radioactive iodine.

Abstract

Stunning of thyroid tissue by diagnostic activities of (131)I has been described by some investigators and refuted by others. The support both for and against stunning has at times been enthusiastic and vigorous. We present the data from both sides of the debate in an attempt to highlight the strengths and deficiencies in the investigations cited. Clinical, animal, and in vitro studies are included. There are considerable differences in clinical practice, such as the administered activity for diagnostic whole-body scan, delay between diagnostic scan and treatment, time between treatment and posttherapy scanning, and timing of follow-up studies, that have to be analyzed with care. Other factors that often cannot be judged, such as levels of thyroid-stimulating hormone and serum iodine at time of diagnostic testing versus treatment could have an influence on stunning. Larger diagnostic doses and longer delays to therapy appear to increase the likelihood of stunning. The stunning effect of early-absorbed radiation from the therapy should also be considered.

Abstract

Only a limited number of studies have evaluated the efficacy of 18F-FDG PET/CT for recurrent cervical carcinoma, which this study seeks to expand upon.This is a retrospective study of 30 women with cervical carcinoma who had a surveillance PET/CT after initial therapy. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were calculated using a 2 × 2 contingency table with pathology results (76%) or clinical follow-up (24%) as the gold standard. The Wilson score method was used to perform 95% confidence interval estimations.The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET/CT for the detection of local recurrence at the primary site were 93, 93, 93, 86, and 96%, respectively. The same values for the detection of distant metastases were 96, 95, 95, 96, and 95%, respectively. Seventy-one percent of the scans performed in symptomatic patients showed true-positive findings. In comparison, 44% of scans performed in asymptomatic patients showed true-positive findings. But, all patients subsequently had a change in their management based on the PET/CT findings such that the effect was notable. The maximum standardized uptake value ranged from 5 to 28 (average: 13 ± 7) in the primary site and 3 to 23 (average: 8 ± 4) in metastases which were significantly different (p = 0.04).This study demonstrates favorable efficacy of 18F-FDG PET/CT for identification of residual/recurrent cervical cancer, as well as for localization of distant metastases.

Abstract

The role of F-FDG PET has been studied in ovarian carcinoma, but its sensitivity and specificity calculations are based on dedicated PET acquisition, not PET/CT in the majority of the published studies. Therefore, we were prompted to review our experience with PET/CT in the management of patients with ovarian carcinoma.This is a retrospective study of 43 women with ovarian carcinoma, 27-80 years old (average: 53.9+/-7.8), who had whole-body PET/CT at our institution from 1 January 2003 to 31 August 2006. We reviewed the patients' outcomes from medical records and compared them to the interpretation of the PET/CT scans. Sensitivity and specificity were calculated using a 2 x 2 table with pathology results (79.1% of the patients) or clinical follow-up (20.9% of the cases) as the 'gold standard'. Confidence interval (CI) estimations were performed using the Wilson score method.All patients had advanced stage ovarian cancer and the study was requested for re-staging. A total of 60 scans were performed: 30 patients had one scan, nine patients had two scans and four patients had three scans. The administered doses of F-FDG ranged from 381.1 to 769.6 MBq (average: 569.8+/-73.3). PET/CT had a sensitivity of 88.4% (95% CI: 75.1-95.4) and a specificity of 88.2% (95% CI: 64.4-97.9) for detection of ovarian cancer. The SUV max of the detected lesions ranged from 3 to 27 (average: 9.4+/-5.9). The CA-125 tumor marker ranged from 3 to 935 kU/ml (average: 265.2) in patients with positive scans and 4-139 kU/ml (average: 17.1) in patients with negative scans. This difference was statistically significant (P value: 0.0242).This study confirms the good results of F-FDG PET/CT for identification of residual/recurrent ovarian cancer, as well as for distant metastases localization. PET/CT should be an integral part in evaluation of patients with high-risk ovarian cancer or rising values of tumor markers (CA-125), prior to selection of the most appropriate therapy.

Abstract

Apart from the common causes of thyrotoxicosis, such as Graves' disease and functioning nodular goiters, there are more than 20 less common causes of elevated free thyroid hormones that produce the symptoms and signs of thyrotoxicosis. This review describes these rarer conditions and includes 14 illustrative patients. Thyrotropin and free thyroxine should be measured and, when the latter is normal, the free triiodothyronine level should be obtained. Measurement of the uptake of (123)I is recommended for most patients.

Abstract

Gallbladder uptake is occasionally encountered with commonly used nonhepatobiliary radiopharmaceuticals. Identification of the biliary tract by a nonhepatobiliary agent can identify disease, such as uptake of labeled white blood cells. However, in most cases, gallbladder uptake of nonhepatobiliary tracers is not due to pathology in these cases. It is important to avoid attributing gallbladder uptake to disease in the gallbladder or adjacent anatomic structures. We present 3 cases of unexpected gallbladder tracer uptake and provide a review of the literature describing incidental gallbladder uptake on nonhepatobiliary nuclear medicine studies. The potential for misdiagnosis and the steps taken to avoid this are discussed.

Treatment of micropapillary carcinoma of the thyroid: Where do we draw the line?THYROIDMcDougall, I. R., Camargo, C. A.2007; 17 (11): 1093-1096

Abstract

Two patients with papillary thyroid cancer were seen in consultation after they had been treated in other medical centers. Their cancers measured 1 and 1.2 mm, respectively. Both patients were treated by two thyroid operations and (131)I ablation. We believe that, apart from lobectomy, these therapies were not justified. We draw attention to this to provide a topic for debate and to attempt to prevent this happening to other patients.

Abstract

There are approximately 32,000 new cases of thyroid carcinoma annually in the United States. F-18 FDG PET/CT has an established role in cancer management, including thyroid cancer, usually in patients who are thyroglobulin (Tg) positive/iodine negative. We reviewed our experience with F-18 FDG PET/CT in thyroid cancer, with an emphasis on correlation with Tg, and maximum standardized uptake values (SUV). We also analyzed the role of thyroid stimulating hormone (TSH) on PET/CT results.This is a retrospective study (January 2003 to December 2006) of 76 patients with differentiated thyroid cancer, who had F-18 FDG PET/CT scans. There were 44 women and 32 men, with age range of 20 to 81 years (average, 51.1 +/- 18.1). The administered doses of F-18 FDG ranged from 396 to 717 MBq (15.8-19.4 mCi) (average, 566 +/- 74.8) (15.3 +/- 2). Reinterpretation of the imaging studies for accuracy and data analysis from medical records were performed.A total of 98 PET/CT scans were analyzed (59 patients had 1 scan, 12 patients had 2, and 5 patients had 3). PET/CT was 88.6% sensitive (95% CI: 78.-94.3) and 89.3% specific (95% CI: 71.9-97.1). Mean Tg level was 1203 ng/mL (range, 0.5-28,357) in patients with positive PET/CT and 9.72 ng/mL (range, 0.5-123.0) in patients with negative PET/CT scans (P = 0.0389). Mean SUV max was 10.8 (range, 2.5-32) in the thyroid bed recurrence/residual disease and 7.53 (range, 2.5-26.2) in metastatic lesions (P = 0.0114). Mean SUV max in recurrent/residual disease in patients with TSH =30 mIU/L was 9.3 (range, 2.5-34.1) and in patients with TSH >30 mIU/L was 8.1 (range, 2.6-32) (P = 0.2994).F-18 FDG PET/CT had excellent sensitivity (88.6%) and specificity (89.3%) in this patient population. Metastatic lesions were reliably identified, but were less F-18 FDG avid than recurrence/residual disease in the thyroid bed. TSH levels at the time of PET/CT did not appear to impact the FDG uptake in the lesions or the ability to detect disease. In the setting of high or rising levels of Tg, our study confirms that it is indicated to include PET/CT in the management of patients with differentiated thyroid cancer.

Abstract

Two patients who were placed on a low-iodine diet in preparation for testing and possible treatment with radio-iodine developed severe hyponatremia that required hospitalization. In elderly patients or those with risk factors for hyponatremia, serum sodium should be measured.

Abstract

Silent thyroiditis, excluding postpartum thyroiditis and destructive amiodarone thyroiditis, is a relatively uncommon cause of thyrotoxicosis and recurrent cases are even rarer. We present four patients with recurrent silent thyroiditis. The number of episodes ranged from two to nine. All four patients had episodes that were similar in duration (4-6 weeks) as well as in their clinical (no viral prodrome or neck pain), biochemical (high total triiodothyronine [T(3)], free thyroxine [T(4)], and low thyrotropin [TSH] presence of antibodies to thyroid antigens), and scintigraphic (low radioiodine uptake) findings. Individual symptoms and symptom-free duration (from 1 to 4 years) were more variable. No associations were found with regard to medications, pregnancies, or other disease states previously implicated in thyroiditis. One patient was unsuccessfully prescribed thyroid hormone to prevent recurrence. Three were treated with radioablative iodine therapy during the recovery phase of an episode; they became hypothyroid and take replacement l-thyroxine. They have remained symptom free.

Abstract

Recombinant human TSH (rhTSH) is used to increase radioiodine uptake during imaging of thyroid cancer, obviating the need to render the patient hypothyroid. We assessed the reproducibility of radioiodine uptake, serum thyrotropin (TSH), and stimulated serum thyroglobulin (Tg) levels after rhTSH administration.A retrospective review was performed of patients at Stanford who underwent whole-body (131)I scanning for surveillance of thyroid cancer twice after thyroidectomy and (131)I ablation, with rhTSH prior to each scan. Forty-eight hour radioiodine uptake, peak serum TSH, and stimulated serum Tg levels for each study were recorded. Paired t tests and correlation analysis were used to assess interexamination repeatability.Twenty-three patients underwent two scintiscans with rhTSH, for a total of 46 exams. There was no significant difference between percent uptake at 48 h in the paired exams (p=0.40). Serum TSH level was measured in 45 of 46 exams; TSH exceeded 50 mIU/l in all cases, and there was no significant difference between paired TSH levels (p=0.93). All patients had stimulated serum Tg levels measured, with no significant difference between paired Tg levels (p=0.40); after excluding one patient whose Tg changed from 15.8 ng/ml to undetectable between scans without interval treatment, the p value rose to 0.95. There was a strong correlation among paired uptake values (r=0.85, p<0.0001), peak serum TSH (r=0.69, p=0.0003), and stimulated Tg levels (r=0.81, p<0.0001). No discordant scan interpretations were reported.Forty-eight hour radioiodine uptake, peak serum TSH, and stimulated serum Tg levels after administration of rhTSH are repeatable between studies, demonstrating reproducibility of diagnostic results without rendering patients hypothyroid.

Abstract

In this review, the causes of thyrotoxicosis and the treatment of syndromes with increased trapping of iodine are discussed. The benefits and the potential side effects of 3 frequently used therapies--antithyroid medications, thyroidectomy, and (131)I treatment--are presented. The different approaches to application of (131)I treatment are described. Treatment with (131)I has been found to be cost-effective, safe, and reliable.

Abstract

18F-FDG PET/CT has rapidly become a widely used imaging modality for evaluating a variety of malignancies, including squamous cell carcinoma of the head and neck and thyroid cancer. Using both published data and the multidisciplinary experience at our institution, we provide a practical set of guidelines and algorithms for the use of 18F-FDG PET/CT in the evaluation and management of head and neck cancer and thyroid cancer.

Abstract

2-Deoxy-2-[F-18]fluoro-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) is widely available as a powerful imaging modality, combining the ability to detect active metabolic processes and their morphologic features in a single exam. The role of FDG-PET is proven in a variety of cancers, including melanoma, but the estimates of sensitivity and specificity are based in the majority of the published studies on dedicated PET, not PET/CT. Therefore, we were prompted to review our experience with FDG-PET/CT in the management of melanoma.This is a retrospective study on 106 patients with melanoma (20-87 years old; average: 56.8 +/- 15.9), who had whole-body FDG-PET/CT at our institution from January 2003 to June 2005. Thirty-eight patients (35.9%) were women and 68 patients (64.1%) were men. Reinterpretation of the imaging studies for accuracy and data analysis from medical records were performed.All patients had the study for disease restaging. The primary tumor depth (Breslow's thickness) at initial diagnosis was available for 76 patients (71.7%) and ranged from 0.4 to 25 mm (average: 3.56 mm). The anatomic level of invasion in the skin (Clark's level) was determined for 70 patients (66%): 3, level II; 13, level III; 43, level IV; 11, level V. The administered dose of (18)F FDG ranged from 9.8 to 21.6 mCi (average: 15.4 +/- 1.8 mCi). FDG-PET/CT had a sensitivity of 89.3% [95% confidence interval (CI): 78.5-95] and a specificity of 88% (95% CI: 76.2-94.4) for melanoma detection.This study confirms the good results of FDG-PET/CT for residual/recurrent melanoma detection, as well as for distant metastases localization. PET/CT should be an integral part in evaluation of patients with high-risk melanoma, prior to selection of the most appropriate therapy.

Abstract

An adrenal metastasis was identified on an F-18 FDG PET/CT scan in a patient with anaplastic thyroid cancer. There are very few reports of thyroid cancer, even anaplastic thyroid cancer, metastasizing to the adrenal.

Abstract

Osseous and soft tissue sarcomas (OSTS) represent a histologic heterogeneous group of malignant tumors. Most of the current clinical data on the role of F-18 FDG PET in sarcomas come from patients studied with dedicated PET and less frequently with hardware fusion PET/CT. Therefore, we were prompted to review our experience with F-18 FDG PET/CT in OSTS.This is a retrospective study (January 2003-December 2005) of 44 patients with histologic diagnoses of OSTS who had F-18 FDG PET/CT at our institution. The group included 22 men and 22 women with an age range of 2 of 84 years (average, 37 +/- 20.2 years). The administered doses of F-18 FDG range 4.1 to 19.5 mCi (average, 14.3 +/- 3 mCi). Reinterpretation of the imaging studies for accuracy and data analysis from medical records was performed.The sensitivity and specificity of combined F-18 FDG PET/CT were 100% (95% confidence interval [CI] = 75.7-100) and 93.3% (95% CI = 78.7-98.1) for the primary OSTS, and 80% (95% CI = 58.4-91.9) and 86.4% (95% CI = 66.7-95.2) for metastases. When interpreted separately, CT outperformed PET for pulmonary metastases detection: CT was 76.5% sensitive and 88% specific, whereas PET was only 57.1% sensitive but 96.4% specific. For detection of other metastases, CT was 82.3% sensitive and 76% specific, with PET demonstrating 78.6% sensitivity and 92.8% specificity.Relatively similar results (except better specificity for PET and PET/CT) were noted when examining the rate of metastases detection, excluding pulmonary lesions. However, CT had a better detection rate for pulmonary metastases when compared with PET alone. A negative PET scan in the presence of suspicious CT findings in the chest cannot reliably exclude pulmonary metastases from OSTS.

Abstract

A 53-year-old man was admitted to the hospital because of tracheal compressive symptoms from a rapidly expanding thyroid mass. The patient first noticed the nodule less than a week prior to admission. Thyroid tests were normal. A fine-needle aspiration (FNA) biopsy showed a monotonous population of intermediate-sized lymphoid cells with scant cytoplasm suspicious for lymphoma. Twelve hours later an emergent computed tomography (CT) scan confirmed left tracheal deviation with compression, however, there were no signs of tumor invasion. The patient received emergent CHOP (clophosphamide, adriamycin, vincristine, prednisone) and rituxan therapy. His mass completely resolved within 36 hours. Bone marrow biopsy provided the final diagnosis of stage IV Burkitt's lymphoma and his therapy was changed to hyper CVAD-R chemotherapy (cytoxan, vincristine, adriamycin, dexamethasone, rituxan). The patient's hospital course was complicated by tumor lysis syndrome that was managed by hydration and allopurinol. To our knowledge, this is only the second reported case of Burkitt's lymphoma presenting as a thyroid mass. His presentation highlights the urgency in diagnosis and provides an opportunity to review a rare type of primary thyroid lymphoma.

Abstract

2-Deoxy-2-[F-18]fluoro-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) is becoming widely available as a powerful imaging modality, combining the ability to detect active metabolic processes and their morphologic features in a single study. The role of FDG-PET/CT is proven in lymphoma, melanoma, colorectal carcinoma, and other cancers. However, there are rare malignancies such as Merkel cell carcinoma that can potentially be evaluated with PET/CT. We were therefore prompted to review our experience with FDG-PET/CT in the management of patients with Merkel cell carcinoma.This is a retrospective case series of six patients with Merkel cell carcinoma, 58-81 years old (average 69 +/- 8.3), who had whole-body PET/CT at our institution from January 1st, 2003 to August 31st, 2005. Two patients were women and four were men. Reinterpretation of the imaging studies for accuracy and data analysis from medical records were performed.Twelve examinations were acquired for the six patients (one patient had six PET/CT, one patient had two PET/CT, and four patients had one PET/CT). The injected FDG doses ranged 381.1-669.7 MBq (average 573.5 +/- 70.3). Four patients had the PET/CT as part of initial staging, and two patients had the exam for restaging (after surgery and XRT). A total of six Merkel lesions (pancreas, adrenal, lip, submandibular lymph nodes, cervical lymph nodes, and parapharyngeal soft tissue) were identified in three patients and confirmed on histopathological examination. The FDG uptake in these areas was intense, with maximum standardized uptake value (SUVmax) values of 5-14 (average 10.4 +/- 3.8). In one patient, the PET/CT scan identified abnormal focal distal sigmoid uptake that was biopsied and diagnosed as adenocarcinoma. Two patients had negative scans and had no clinical evidence of disease on follow-up office visits (up to one year after PET/CT).This case series suggests that FDG-PET/CT may have a promising role in the management of patients with Merkel cell carcinoma.

The role of radioactive iodine in the treatment of well-differentiated thyroid cancerSURGICAL ONCOLOGY CLINICS OF NORTH AMERICAWeigel, R. J., McDougall, I. R.2006; 15 (3): 625-?

Abstract

The prognosis in differentiated thyroid cancer is excellent. The completeness of thyroidectomy and removal of involved regional metastases are the most important elements of management. Iodine 131 has a role in ablating residual thyroid and treating regional and distant metastases. The effectiveness of the treatment is confirmed by negative follow-up scans and low or undetectable Tg. This therapy is relatively specific, but other tissues can receive meaningful doses of radiation and acute and long-term complications can occur. Therefore, whether the patient will have a better prognosis after treatment with 131I and whether the benefits of treatment are greater than the side effects must be determined for every patient.

Abstract

A 58-year-old woman was found to have metastatic thyroid cancer in her liver. This was identified when she was investigated for upper abdominal pain and underwent biopsy of hepatic lesions. She had no palpable thyroid nodule and had a normal ultrasound of the thyroid. Previously, both ovaries had been removed because of tumors. The pathologic findings in one of the ovaries could not be recovered because the procedure was more than 40 years ago, when the patient was a teenager. By a process of elimination, a diagnosis of metastatic struma ovarii was established. Treatment of metastatic thyroid cancer from struma ovarii, including removal of the normal thyroid and administration of I-131, is presented.

Abstract

123I has been promoted for diagnostic imaging as a means of avoiding 'stunning'. It has also been suggested that the more favourable physical characteristics and consequent enhanced imaging resolution provided by 123I offers a more accurate diagnostic assessment of the extent of disease prior to therapy. This study evaluated pairs of diagnostic 123I and post-therapy 131I scans for differences in patterns of radioiodine uptake.Thirty-eight patients (31 women and seven men) with a history of differentiated thyroid cancer underwent 41 diagnostic 123I studies. 131I therapy was administered to 29 patients as soon as possible after positive diagnostic findings were confirmed (with one patient being treated twice during the study period, making 30 treatments). Post-treatment scans were obtained an average of 5.8 days after therapy.Qualitative comparison of diagnostic 123I and post-therapy 131I scans revealed a decrease in the extent of post-treatment uptake in four of the 30 treatments (13%). Seven patients (23%) demonstrated increased uptake on their post-therapy 131I scan.Because the physical characteristics of 123I make it inconceivable that it could cause stunning, the decrease in post-treatment uptake seen in 13% of patients from this series increases the likelihood that this pattern is due to factors other than stunning, such as differential rates of radioiodine turnover. In addition, the increase in extent of post-therapy uptake seen in 23% of patients suggests that diagnostic imaging with 123I is vulnerable to the same pre-therapy staging inaccuracies as is low-dose diagnostic imaging with 131I. Further work is needed to determine whether larger diagnostic doses of 123I might mitigate this problem.

Abstract

To determine the relative frequency of various sonographic findings in papillary carcinoma of the thyroid.We retrospectively analyzed the sonographic features in 55 patients with proven papillary carcinoma of the thyroid. Sonographic features analyzed were echo texture, cystic change, margin, contour, presence of a peripheral halo, vascularity, and calcification pattern. Features were classified as common (> or = 35% of cases) or uncommon (< 10% of cases). Combinations of features were also analyzed.Common sonographic features of papillary carcinoma included hypoechoic texture (86%), microcalcifications (42%) or no calcifications (47%), well-defined margins (47%), and intrinsic hypervascularity (69%). Uncommon features included hyperechoic or mixed echo texture, cystic elements, irregular margins, hypovascularity, and coarse or peripheral calcifications. Of the 29 lesions that had calcifications, 20 (69%) had microcalcifications; 5 (17%) had coarse calcifications; and 1 had peripheral calcifications. In total, 54% of cases had at least 1 uncommon feature, and 11% had 2 or more uncommon features. Cystic carcinomas were rare and accounted for only 6% of lesions; all had hypervascular solid components. No carcinomas in our series were completely avascular.There is a broad spectrum of sonographic findings in papillary carcinoma of the thyroid. Half of the lesions in this series had at least 1 uncommon sonographic feature.

Abstract

The outcome in differentiated thyroid cancer is excellent. Simple prognostic factors, including the age of the patient at diagnosis, the size of the primary cancer, completeness of surgical excision, and the presence of distant metastases, allow the clinician to judge how a patient will do. The preferred treatment is total thyroidectomy and in selected patients radioactive iodine can be used to ablate residual thyroid or functioning metastases in lymph nodes and distant sites. The physician has two excellent methods for following the patient: the whole-body scan with radionuclides of iodine, and measurement of serum thyroglobulin. In patients with elevated thyroglobulin and negative scans with radioactive iodine, there is increasing evidence that positron emission tomography (PET) is helpful in locating the site of thyroglobulin production.

Abstract

Radioiodine has aided the management of differentiated thyroid cancer for several decades. Most thyroid cancers retain the ability to trap iodine, and radionuclides of iodine can be used both diagnostically and therapeutically. The availability of sensitive diagnostic tests, coupled with the ability to deliver targeted therapy, gives physicians the ability to manage thyroid cancer better than with any other type of cancer. The correct interpretation of radioiodine scans is critical in the appropriate management of patients with thyroid cancer. False positive findings do occur. A radioiodine scan showing abnormal uptake outside the thyroid bed must be studied carefully and alternative reasons for the finding must be considered. The scan should be analysed systematically. Is there residual thyroid? If so, what is the 48 or 72 h neck uptake? Radioiodine uptake in the salivary glands, stomach, gastrointestinal and urinary tracts should be acknowledged as physiological. Diffuse uptake is seen in the liver in most patients with functioning thyroid at the time of their post-therapy scan. When there is uptake of the radioiodine outside these regions, contamination must be considered. A variety of cases illustrating true positive, true negative, and false positive findings is presented in this review, and the causes and consequences of misinterpretation of radioiodine scans are discussed.

Abstract

Ectopic intrathyroidal thymomas are an exceedingly rare clinical entity that can be challenging to diagnose. This report describes a 39-year-old Japanese woman who presented with prominent left-sided thyroid enlargement that was thought to be a dominant thyroid nodule by ultrasound. Two fine-needle aspiration biopsies showed an atypical lymphoid proliferation that was suspicious for although not diagnostic of a low-grade lymphoma. A diagnosis of ectopic intrathyroidal thymoma was made only after appropriate histopathologic assessment of the surgical specimen.

Abstract

Surgical resection is the only curative treatment option for locoregional recurrence of well-differentiated thyroid cancer that does not trap radioiodine. We hypothesized that intraoperative ultrasonography would aid in the localization of recurrent thyroid cancer and would enhance the ability to perform a complete resection.Between June 2000 and October 2001, 13 patients with recurrent, scan-negative, papillary thyroid cancer were explored by using intraoperative ultrasonography.All patients had identification and resection of recurrent papillary thyroid cancer. Eleven patients had a complete resection, and 2 patients had incomplete resection as a result of local invasion. Ultrasound was required for identification of tumor in 7 patients and included all patients with a history of external beam radiotherapy. In 6 of these 7 patients, the tumor was paratracheal or invasive into the trachea or thyroid cartilage. In 11 patients with detectable serum thyroglobulin preoperatively, the level demonstrated a decline in 10 patients and became undetectable in 7 patients.Intraoperative ultrasonography is a useful method to identify nonpalpable, locoregional recurrences of thyroid cancer. Ultrasound was particularly helpful in patients who had previous external beam radiotherapy and in the identification of tumor nodules of 20 mm or less that were invasive or adherent to the airway.

Abstract

Dissemination of tumor cells from needle biopsy has been observed in a wide range of tumor types. Fine needle aspiration (FNA) biopsy has become accepted as the first-line test in the evaluation of thyroid nodules. Local recurrence of thyroid cancer from needle track seeding is an extremely rare complication of thyroid FNA.A 59-year-old woman developed local recurrence of papillary thyroid carcinoma three years after FNA of the primary cancer. Local metastases developed in the skin and sternocleidomastoid muscle. The location of the recurrent cancer and the linear relationship of the metastases indicated that local recurrence was due to needle track seeding at the time of FNA.Needle track seeding has been recognized as a possible, albeit rare, complication of FNA of thyroid cancer. Although proper FNA technique can reduce the potential for needle track seeding, its occurrence is an unavoidable complication of FNA evaluation of thyroid malignancies.

Abstract

To determine the long-term outcome of radiotherapy (RT) in patients with progressively symptomatic thyroid eye disease and to evaluate the potential long-term sequelae.Four hundred fifty-three patients provided written informed consent and received retrobulbar RT for Graves' ophthalmopathy at Stanford University Medical Center; 197 with 1 year of follow-up were retrospectively analyzed. Of the 197 patients, 189 received RT to the bilateral retrobulbar regions, and 4 received unilateral RT. The technical information was unavailable for 4 patients. Patients were assessed by chart review, telephone interview, questionnaire, and multidisciplinary physician examination. Eye impairment was scored using the SPECS system. The end point review included the before and after treatment SPECS score, surgical intervention, and patient satisfaction. Potential complications, including cataract development, retinopathy, and tumor formation, were investigated. Multivariate analyses were performed to assess the prognostic variables.Improvement or resolution was 89% for soft-tissue findings; 70% for proptosis; 85% for extraocular muscle dysfunction; 96% for corneal abnormalities; and 67% for sight loss. The response to RT may take >6 months to stabilize. Factors predictive of response varied in the individual SPECS categories but included the initial SPECS score, pretreatment thyroid status, female gender, a 20-Gy RT dose, and a history of hypertension. Nonpredictive factors included a history of tobacco use, diabetes mellitus, steroids, and prior cataracts. Only 16% required surgical intervention to preserve their vision or restore binocular vision. Twenty-two patients (12%) developed cataracts after irradiation (median 11 years). No patient developed a tumor within the RT field during the follow-up period (range 1-29 years). Ninety-eight percent of patients were pleased with their results, and 2% believed their symptoms progressed despite RT.Retrobulbar irradiation (20 Gy) is safe and effective treatment for progressive Graves' ophthalmopathy, with a 96% overall response rate, 98% patient satisfaction rate, and no irreparable long-term sequelae, with follow-up extending 29 years. The most common late effect observed was cataract development, which occurred more frequently in older patients and was reversible with extraction. Elective surgical intervention after RT should be withheld until patients have demonstrated a plateau in response.

Abstract

Research on the relationship between iodine exposure and thyroid cancer risk is limited, and the findings are inconclusive. In most studies, fish/shellfish consumption has been used as a proxy measure of iodine exposure. The present study extends this research by quantifying dietary iodine exposure as well as incorporating a biomarker of long-term (1 year) exposure, i.e., from toenail clippings. This study is conducted in a multiethnic population with a wide variation in thyroid cancer incidence rates and substantial diversity in exposure. Women, ages 20-74, residing in the San Francisco Bay Area and diagnosed with thyroid cancer between 1995 and 1998 (1992-1998 for Asian women) were compared with women selected from the general population via random digit dialing. Interviews were conducted in six languages with 608 cases and 558 controls. The established risk factors for thyroid cancer were found to increase risk in this population: radiation to the head/neck [odds ratio (OR), 2.3; 95% confidence interval (CI), 0.97-5.5]; history of goiter/nodules (OR, 3.7; 95% CI, 2.5-5.6); and a family history of proliferative thyroid disease (OR, 2.5; 95% CI, 1.6-3.8). Contrary to our hypothesis, increased dietary iodine, most likely related to the use of multivitamin pills, was associated with a reduced risk of papillary thyroid cancer. This risk reduction was observed in "low-risk" women (i.e., women without any of the three established risk factors noted above; OR, 0.53; 95% CI, 0.33-0.85) but not in "high-risk" women, among whom a slight elevation in risk was seen (OR, 1.4; 95% CI, 0.56-3.4). However, no association with risk was observed in either group when the biomarker of exposure was evaluated. In addition, no ethnic differences in risk were observed. The authors conclude that iodine exposure appears to have, at most, a weak effect on the risk of papillary thyroid cancer.

Abstract

We report three cases of papillary thyroid carcinoma occurring after successful treatment of osteosarcoma. Only one of the three patients received radiation therapy (to the chest) as part of the primary treatment of osteosarcoma. The onset of thyroid carcinoma occurred between 8 and 16 years from the cessation of osteosarcoma therapy. All patients are alive and disease-free from both malignancies. Whereas the association between osteosarcoma and thyroid carcinoma has not previously been recognized, there have been five case reports of these two entities occurring in the same patient. Three of these cases occurred in patients with Werner syndrome. None of the patients reported here had physical stigmata of Werner syndrome or a family history consistent with a hereditary cancer syndrome. Thyroid carcinoma occurs infrequently in patients with osteosarcoma, but in view of the rarity of these two disorders, this association may represent an inherited predisposition to these malignancies.

Abstract

The role of Positron Emission Tomography (PET) using 18F-fluorodeoxyglucose (FDG) in the management of thyroid cancer is discussed. It is important to ensure that patients are relaxed because uptake of FDG in tense or active muscles in the neck and larynx can be misinterpreted as metastases. The major role for PET is in patients where the stage of disease is uncertain, usually the result of discordant negative 131I scan and a positive serum thyroglobulin (Tg) values. PET identifies the source of Tg production in 50-80% of patients. PET scan can be negative in well differentiated cancers which retain the ability to trap iodine. This can result in a 'flip/flop', with negative PET, positive radio-iodine scan, or positive PET, negative radioiodine scan. PET is also valuable in identifying the source of calcitonin production in patients with medullary thyroid cancer. When focal uptake is seen in the thyroid of patients who are scanned for non thyroidal reasons, the likelihood of primary thyroid cancer is high. In contrast diffuse uptake of FDG in the thyroid is usually the result of auto-immune thyroid disorders.

Abstract

Advances in measurement of thyroglobulin (Tg) and in imaging techniques including high resolution ultrasound, magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) scan have increased our ability to detect thyroid cancer recurrences at an earlier stage. (1,2) After thyroidectomy, patients are often treated with radioiodine, but the recurrent cancers may not image with radioiodine. In these instances, the only definitive treatment is surgical resection. Reoperative neck surgery can be challenging, especially when trying to find a small cancer nodule within the central neck that contains dense fibrotic scar tissue. Herein we describe the use of intraoperative ultrasonography to identify the location of recurrent thyroid cancer. This technique can aid in tumor localization and may help to avoid complications such as recurrent nerve injury.

Abstract

Radioiodine has been shown to reduce recurrences and improve survival in well-differentiated thyroid cancer. To maximize the effectiveness of radioiodine therapy, patients are first treated by total thyroidectomy and then allowed to become hypothyroid. The elevation of thyroid-stimulating hormone, or thyrotropin (TSH), that occurs with hypothyroidism stimulates uptake of radioiodine in normal and cancerous thyroid tissues. A recent advance has been the introduction of recombinant human TSH (rhTSH), which is administered intramuscularly prior to testing with radioiodine. Phase III trials have demonstrated that rhTSH stimulates both uptake in and production of thyroglobulin by thyroid cells and the results are comparable to those of hypothyroid protocols in the majority of patients. Patients prefer the rhTSH protocol because they continue to ingest exogenous thyroid hormone and the symptoms of hypothyroidism are avoided. The rhTSH protocol is preferable in patients with pituitary dysfunction and in those who cannot tolerate hypothyroidism. RhTSH can also allow treatment of patients who have not had an adequate thyroidectomy and who are poor candidates for reoperation.

Abstract

Radiation sialadenitis is a complication of I-131 therapy for thyroid cancer. They authors report a case of intense uptake by parotid glands in a diagnostic I-131 scan (2 mCi) in whom sialadenitis had developed previously after a 100-mCi dose of I-131. Similar examples of images could not be found in the literature.

Abstract

Recombinant human thyrotropin (rhTSH) has been evaluated in 38 patients with differentiated thyroid cancer. The patients had all been treated previously by operation and 31 had received radioiodine 131I. The patients continued to take thyroid hormone and changed to a low iodine diet for 14 days before and throughout the week of testing. The rhTSH was injected intramuscularly on two consecutive days, 74 MBq 131I was administered on the next day and scintigraphy completed 48 h after that. TSH was measured before administration of 131I, and thyroglobulin after the scan. All patients preferred this method to withdrawal of thyroid hormone, but 45% had mild symptoms including headache and nausea. The average TSH was 127 mU x l(-1), and was inversely related to the weight of the patients. Thirty-four had negative scans with a mean uptake of 0.06%. Thyroglobulin values above 10 ng x ml(-1) were found in seven patients, of whom four had similar findings when scanned after withdrawal of thyroid hormone. Of four with positive scans, two had undetectable thyroglobulin. The rate of clearance of 131I was compared in patients studied at 72 h who were hypothyroid and at 48 h in euthyroid patients given rhTSH and was found to be longer in the latter. We conclude that rhTSH can be used to stimulate thyroid tissue to trap 131I and secrete thyroglobulin. Both scan and thyroglobulin should be obtained. The method is well tolerated.

Abstract

Systemic unsealed radiation therapy is achieved when a radioactive substance is administered orally or parenterally and that material is concentrated in an organ or site for sufficient time to deliver a therapeutic dose of radiation. The radioactive material usually emits beta particles. In general, there is intense local radiation of the abnormal tissues, and normal organs, which do not trap the radioactive material, are exposed to a small radiation dose. The most frequent treatments involve radioiodine (131)I for hyperthyroidism and differentiated thyroid cancer. Other applications include treatment of painful skeletal metastases, polycythemia vera, malignant cysts, and neuroendocrine tumors. The treatments are usually well tolerated and not associated with long-term effects, such as cancer or infertility.

Abstract

High-resolution ultrasound and technetium Tc 99m sestamibi scanning can be used for preoperative localization of abnormal parathyroid glands in patients with hyperparathyroidism.Ultrasound and sestamibi scanning were performed in patients undergoing neck exploration for hyperparathyroidism. If the 2 scans agreed in identifying a single adenoma, and surgery confirmed the location of a single adenoma and an ipsilateral normal gland, a unilateral exploration was performed.University tertiary care center.Sixty-one consecutive patients undergoing surgery for hyperparathyroidism from September 1, 1994, through September 30, 1997.High-resolution ultrasound was performed in 59 patients and sestamibi scanning in 58 patients; all patients underwent neck exploration by a single surgeon.The results of preoperative ultrasound and sestamibi scanning were compared with operative and histological findings.All patients were cured of hypercalcemia. Specificity of ultrasound and sestamibi scanning was 98% and 99%, respectively; however, their sensitivity was only 57% and 54%, respectively. Both imaging modalities had lower sensitivities in the setting of multigland disease. If both imaging studies were considered as a single test, sensitivity for imaging in patients with primary hyperparathyroidism reached 78%. Our localization protocol allowed a unilateral approach in 43% of patients (23 of 53).These results confirm the value of preoperative localization in patients with hyperparathyroidism. A unilateral approach can be used with a high degree of success in cases when ultrasound and sestamibi scanning agree in the identification of a single adenoma confirmed by surgical exploration with the identification of a normal ipsilateral gland.

Abstract

The distribution and nasal clearance of 99Tcm-labelled albumin (18.5 MBq), used as a mucosal vaccine surrogate for FluMist, was determined in three volunteers. The subjects were randomized in a cross-over clinical study design to receive either large-particle aerosal (nasal spray) followed by nose drops, or nose drops followed by the nasal spray, 1 week apart. Gamma scintigraphy was used to measure the distribution and clearance. The 'vaccine' delivered as drops was cleared from the nose into the oesophagus and upper stomach at very variable rates. In contrast, the nasal spray was uniformly distributed and cleared from the nasopharynx with a 50% mean clearance time of 50 min (range 40-60 min) and was not detected in the lungs.

Abstract

Focal uptake of I-131 in the region of the liver was seen on whole-body scans in a 22-year-old asymptomatic woman who had invasive papillary cancer. Hepatic metastases were unlikely because of the clinical risk factors, and a CT scan of the liver was normal. By superimposing the I-131 scintiscan and a hepatobiliary scan, the site of the uptake was shown to be in the biliary tract, and it had migrated to the gallbladder on more delayed images. No pathologic cause was found.

Abstract

We evaluated 10 patients with suspected recurrent papillary thyroid cancer using [18F]fluorodeoxyglucose positron emission tomography (FDG PET). Prior therapy included total (n = 8) or subtotal (n = 2) thyroidectomy, radiation therapy (n = 2) and radioiodine ablation (n = 2). All patients had an 131I scan and one or more of the following imaging studies: 99Tcm-sestamibi scan. 111In-octreotide scan, sonography (US), computed tomography (CT) and magnetic resonance imaging (MRI). Both the PET and 131I scans were negative in four patients. The PET and 131I scan results were discordant in six patients. Of the six discordant cases, five had true-positive PET scans and false-negative 131I studies. Three of these patients underwent neck lymph node dissection that showed positive histology for metastatic papillary carcinoma. Another patient had fine-needle aspiration (FNA) of a parapharyngeal mass that was also positive for papillary carcinoma. One patient was treated with radiation to the thyroid surgical bed based on an elevated serum thyroglobulin and a positive PET finding. Tumour response with a decrease in the size of the lesion was documented by a follow-up MRI scan. The remaining patient had a presumed false-positive PET scan, since a difficult hypocellular FNA of a small palpable lymph node was negative for tumour. We conclude that FDG PET is useful in the evaluation of patients with suspected recurrent papillary thyroid cancer when the 131I scan is negative.

Abstract

The purpose of this study was to determine the impact of ultrasound-guided fine-needle aspiration biopsy (USFNA) in the cytological diagnosis of nodular thyroid disease. It remains unclear exactly what role USFNA should play in the cytological diagnosis of nodular thyroid disease. All patients who underwent fine-needle aspiration (FNA) for nodular thyroid disease at Stanford University Medical Center from 1991 to 1996 were included in the study. Histopathologic diagnoses were compared to cytological diagnoses for those patients who underwent surgery. FNA was performed on a total of 497 thyroid nodules. Palpation-guided FNA (pFNA) was performed on 370 nodules, and USFNA was done on 127. The USFNAs were performed for the following reasons: 95 (75%) for nonpalpable or difficult-to-palpate nodules; 14 (11%) for previously failed FNA; and 18 (14%) for incidentally detected nodules. FNA had an unsuccessful biopsy rate of 16% and a sensitivity and specificity of 89% and 69%, respectively. USFNA had an unsuccessful biopsy rate of 7% and a sensitivity and specificity of 100% and 100%, respectively. The cancer yield at surgery for pFNA was 40%, and the cancer yield at surgery for USFNA was 59%. The complementary use of USFNA with pFNA improves the diagnostic approach to nodular thyroid disease. The use of USFNA has increased the cancer yield at surgery and the sensitivity of thyroid biopsy at our institution.

Abstract

Several aspects of the management of differentiated thyroid cancer cause considerable controversy. Among these is the role of 131I therapy in patients after thyroidectomy. There is no controlled study to demonstrate whether this treatment reduces the recurrence rate or improves mortality. Because of the overall excellent prognosis, it is unlikely that a controlled study will ever be conducted. Most frequently, patients have a diagnostic scan with 131I to determine whether radioiodine would be an appropriate therapy and to judge much to be prescribed, based on the extent of abnormalities seen on the scintiscan. Serum thyroglobulin (Tg) has been found to be a valuable tumor marker, with very good sensitivity and specificity. In most patients, the result of whole-body 131I scintiscan and Tg measurement give concordant results. However, in some patients, Tg is measurable, but the diagnostic scan with 131 is normal. There has been data published about treatment of these patients with therapeutic doses of 131I. The author questions whether this treatment is appropriate, prompted by seeing and hearing of patients who were treated with therapeutic doses of 131I, but had no abnormal uptake of the therapeutic doses and who had no improvement in serum Tg level. These patients have no clinical evidence of disease, and the only abnormality is measurable Tg. Since large doses of radioiodine are not without problems, a controlled clinical trial should be developed to evaluate efficacy in this situation.

Abstract

Altogether, 147 scintiscans, completed 48-72 h after 74 MBq 131I, were compared with scintiscans obtained on average 7.8 days after therapeutic doses of 131I. The therapeutic doses ranged from 1100 to just over 7400 MBq. The reasons for the investigation were to determine (1) if the diagnostic dose interfered with uptake of the therapeutic dose and (2) how often more lesions, or greater extent of disease, was seen on the images using the larger therapy dose. The post-treatment scan showed less uptake in one region in 2 of the 147 patients (1.4%). The post-treatment scan showed more lesions in 12 patients (8%). In eight patients, the extent of disease, but not the stage of disease, was greater. In four patients, the stage of disease was increased, three due to lung uptake on the post-treatment scan which was not seen on the diagnostic scan and one due to uptake in lymph nodes on the post-treatment scan which was not present on the diagnostic scan. 74 MBq 131I seldom interferes with subsequent therapy and seldom underestimates the extent of thyroid cancer. It would appear to be an appropriate dose for diagnostic scintigraphy.

Abstract

To determine the usefulness of radioaerosol ventilation scans for the detection and localization of air leaks from the lungs or bronchial tree.Selected patients with suspected air leaks underwent ventilation scans. Retrospective analysis of data was carried out.Twenty-eight hospitalized patients were included in the study.Ventilation scintigraphy using 99mTc-DTPA (technetium aerosol) was carried out in patients with air leaks.Of the total group, there were 50% true-positive scans, 36% true-negative scans, and 14% false-negative scans giving a sensitivity of 78%, specificity of 100%, and accuracy of 86%.99mTc-DTPA ventilation scintigraphy is useful in some patients with air leaks from the lung or tracheobronchial tree and may help to guide surgical intervention should this become necessary.

Abstract

Persistent fever in a 60-yr-old man with polycystic kidney and liver diseases and bilateral hip prostheses was presented in this study. Multiple diagnostic tests failed to localize a source of infection. Subsequently, a combination of a 111In-oxine labeled WBC and 99mTc-sulfur colloid scans (and computer subtraction) demonstrated abnormally increased WBC activity in the left lobe of the liver, thus, diagnosis of an infected cyst (or cysts) was made. The patient responded to the treatment with antibiotics. This article discusses the clinical features of polycystic disease of the liver and kidneys. Infection in cysts are discussed as well as radiographic and scintigraphic investigations that can be used to diagnose and localize infection in a cyst.

Abstract

A set of minimum clinical guidelines for use by primary care physicians in the evaluation and management of patients with thyroid nodules or thyroid cancer was developed by consensus by an 11-member Standards of Care Committee (the authors of the article) of the American Thyroid Association, New York, NY. The participants were selected by the committee chairman and by the president of the American Thyroid Association based on their clinical experience. The committee members represented different geographic areas within the United States, to reflect different practice patterns. The guidelines were developed based on the expert opinion of the committee participants, as well as on previously published information. Each committee participant was initially assigned to write a section of the document and to submit it to the committee chairman, who revised and assembled the sections into a complete draft document, which was then circulated among all committee members for further revision. Several of the committee members further revised and refined the document, which was then submitted to the entire membership of the American Thyroid Association for written comments and suggestions, many of which were incorporated into a final draft document, which was reviewed and approved by the Executive Council of the American Thyroid Association.

What is the role of 1100 MBq (<30 mCi) radioiodine I-131 in the treatment of patients with differentiated thyroid cancer?NUCLEAR MEDICINE COMMUNICATIONSVanWyngaarden, M., McDougall, I. R.1996; 17 (3): 199-207

Abstract

Based on pre-therapy whole-body 131I scintiscans showing only residual thyroid, 64 patients with differentiated thyroid cancer were treated with 1100 MBq ( < 30 mCi) 131I as out-patients. A follow-up whole-body scan with uptake measurements was made 6-12 months later. An uptake of 10%, this fell to 59%. A serum TSH > 10 microU ml-1 at the time of the first scan was associated with ablation (i.e. an uptake of < or = 0.3% on the follow-up scan) in 93% of patients. We recommend measurement of TSH and a whole-body scan to exclude regional or distant metastases, plus calculation of uptake in the neck to determine whether out-patient therapy with 1100 MBq is appropriate.

Abstract

Whole-body scintigraphy with radioiodine-131 is an important diagnostic test in the management of patients with differentiated thyroid cancer who have undergone surgical treatment. The scan can demonstrate the presence of residual thyroid or functioning metastases in lymph nodes or distant sites. However, there are a number of potential pitfalls in the interpretation of this scan that could lead to a false-positive diagnosis of cancer. The scintiscans are presented for five patients in whom uptake outside of the thyroid was not due to functioning metastases. Some of these abnormalities are physiologic, such as uptake of iodine in the gastrointestinal tract. A comprehensive list of false-positive results are tabulated.

Abstract

There have been several published reports that hypothyroid women do not need to increase the dose of levothyroxine when they become pregnant.For this study, 20 pregnant women who were hypothyroid as a result of surgical thyroidectomy, radio-iodine therapy, or combination therapy were followed for the duration of their pregnancies. These patients were seen regularly, and evaluated clinically and by measurement of free thyroxine (FT4) and thyrotropin (thyroid-stimulating hormone [TSH]).The amount of levothyroxine that was adequate in the nonpregnant state was found to be inadequate during pregnancy. The dosage of levothyroxine given to these patients was increased by an average of 36 micrograms and returned to earlier levels after delivery. There was considerable individual variation in the requirement for additional levothyroxine during pregnancy.For hypothyroid pregnant patients, thyroid function tests, especially TSH, are recommended during each trimester to determine the need for additional levothyroxine.

Abstract

The thyroid gland is the largest pure endocrine gland in the body and one of the organs most likely to produce clinically significant abnormalities after therapeutic external radiation. Radiation doses to the thyroid that exceed approximately 26 Gy frequently produce hypothyroidism, which may be clinically overt or subclinical, as manifested by increased serum thyrotropin and normal serum-free thyroxine concentrations. Pituitary or hypothalamic hypothyroidism may arise when the pituitary region receives doses exceeding 50 Gy with conventional, 1.8-2 Gy fractionation. Direct irradiation of the thyroid may increase the risk of Graves' disease or euthyroid Graves' ophthalmopathy. Silent thyroiditis, cystic degeneration, benign adenoma, and thyroid cancer have been observed after therapeutically relevant doses of external radiation. Direct or incidental thyroid irradiation increases the risk for well-differentiated, papillary, and follicular thyroid cancer from 15- to 53-fold. Thyroid cancer risk is highest following radiation at a young age, decreases with increasing age at treatment, and increases with follow-up duration. The potentially prolonged latent period between radiation exposure and the development of thyroid dysfunction, thyroid nodularity, and thyroid cancer means that individuals who have received neck or pituitary irradiation require careful, periodic clinical and laboratory evaluation to avoid excess morbidity.

Abstract

To develop a set of minimum clinical guidelines for use by primary care physicians in the evaluation and management of patients with hyperthyroidism and hypothyroidism.Guidelines were developed by a nine-member ad hoc Standards of Care Committee of the American Thyroid Association (the authors of this article). The participants were selected by the committee chair and the president of the American Thyroid Association on the basis of their clinical experience. The committee members represented different geographic areas within the United States, in order to take into account different practice styles.Guidelines were developed on the basis of expert opinion of the participants, as well as on available published information.Input was obtained from all of the participants, each of whom wrote an initial section of the document. A complete draft document was then written by three participants (P.A.S., D.S.C., and E.G.L.) and resubmitted to the entire committee for revision. The revised document was then submitted to the entire membership of the American Thyroid Association for written comments, which were then reviewed (mainly by P.A.S., D.S.C., and E.G.L.). Many of the suggestions of the American Thyroid Association members were incorporated into the final draft, which was then approved by the Executive Council of the American Thyroid Association. The entire process, from initial drafts to final approval, took approximately 18 months.A set of minimum clinical guidelines for the diagnosis and treatment of hyperthyroidism and hypothyroidism were developed by consensus of a group of experienced thyroidologists. The guidelines are intended to be used by physicians in their care of patients with thyroid disorders, with the expectation that more effective care can be provided, and at a cost savings.

Abstract

Metastatic papillary carcinoma was diagnosed in a 42-year-old woman. The cancer had invaded out of the gland and was present in many lymph nodes. After her surgical procedure, she was advised to have radioiodine. However, the patient had total renal failure and was on dialysis. Studies were carried out using a tracer dose of 2 mCi of radioiodine, demonstrating that approximately 60% of the radioactivity in the body was removed with each dialysis. Calculations indicated that a meaningful dose of radiation could be delivered to residual thyroid and metastases with 100 mCi of radioiodine and the total body radiation would be < 100 rad delivered over several days. Based on these analyses, she received 100 mCi of I-131 on two separate occasions and on follow-up scan, clinical evaluation and thyroglobulin measurement is free of disease.

Abstract

It can be difficult to localize or even lateralize the site of persistent bronchopleural fistula in patients who have undergone thoracotomy. If the site of persistent air leak can be identified noninvasively, it may be possible to repair the leak with thoracoscopic techniques and thereby avoid repeat thoracotomy. This article reports experience using 99mTc-DTPA ventilation scintigraphy to localize persistent bronchopleural fistulas in six patients. The site of bronchopleural fistula was identified in four patients. In the other two patients, no leak was identified, and the clinical course confirmed that a significant bronchopleural fistula did not exist.

Abstract

There is considerable literature on the effect of pregnancy on established thyroid cancer. In contrast, there are only isolated case reports of management of thyroid cancer diagnosed de novo during pregnancy. We describe four such patients. We recommend fine-needle aspiration biopsy (FNA) of solitary thyroid nodules found early in pregnancy. When the cytopathology is diagnostic of thyroid cancer, thyroidectomy under local or general anesthesia is advised. The patient should be given levothyroxine in a dose sufficient to keep serum thyroid-stimulating hormone (TSH) low. Serum thyroglobulin is a valuable noninvasive method of evaluating completeness of this therapy. The work-up of a nodule found late in pregnancy is best deferred until after delivery.

Abstract

We report the history of a 44-year-old woman, who had four episodes of thyrotoxicosis in 4 years. The clinical findings and laboratory results were all indicative of recurrent silent thyroiditis. Because silent thyroiditis is self-limiting, treatment is usually symptomatic. In this patient radioiodine therapy was eventually prescribed to obviate further recurrences. We were unable to find reports of this number of recurrences.

THE ROLE OF FUNCTIONAL IMAGING IN NEOPLASMS OF THE THYROIDCRITICAL REVIEWS IN CLINICAL LABORATORY SCIENCESMELLO, A. M., McDougall, I. R.1992; 29 (2): 117-139

Abstract

Iodine-123 and Iodine-131 have suitable physical properties that enable them to be used for functional imaging of the thyroid. Iodine-123 is used for routine testing for hyperthyroidism and thyroid nodules, whereas I-131, which has a longer half-life, is used for whole body imaging for detecting metastatic thyroid cancer in patients who have undergone thyroidectomy. The radionuclides of iodine are trapped and organified like nonradioactive iodine. In contrast, technetium as pertechnetate is trapped by the thyroid and can be used for imaging immediately after intravenous injection. There can be differences in scintiscans made in the same patient using radioiodine vs. technetium. Thallium is a useful adjuvant imaging agent for thyroid cancer. It should be stressed that correlation with the clinical findings and biochemical thyroid function tests are very important when evaluating thyroid scintiscans.

Abstract

A small encapsulated papillary thyroid cancer was found in a patient who had received I-131 therapy for Graves' disease 31 months previously. The relationship of Graves' hyperthyroidism and thyroid cancer is discussed, as well as the possible role of I-131 as a cause of the cancer. The published data do not support I-131 as an etiology. The patient is clinically well and cured of both hyperthyroidism and the cancer.

Abstract

Follow-up evaluation of patients who have undergone radical prostatectomy routinely consists of serial bone scintigraphy and, more recently, prostate-specific antigen (PSA) levels. The utility of serial bone scans in combination with PSA levels is retrospectively reviewed in 118 men treated by radical prostatectomy for clinical Stage A or B disease who, at the time of surgery, had no evidence of metastatic disease. Of the 118 patients, 75.4% had no abnormality on either test (mean follow-up 32.4 mo), 9.3% demonstrated a detectable or rising PSA level with negative bone scan (mean follow-up 35 mo), and 8.5% exhibited a detectable and or rising PSA level and positive bone scan (mean follow-up 30.7 mo). Follow-up bone scans were read as either positive or indeterminate with undetectable PSA levels in 6.8% of patients (mean follow-up 27.3 mo). Critical review of the equivocal studies suggests that postoperative PSA levels more truly represent the clinical situation than bone scans. Following radical prostatectomy, routine bone scintigraphy provides little additional information when PSA levels are negative. If PSA becomes detectable or the patient develops symptoms, bone scintigraphy should then be performed.

Abstract

Platelet deposition at the site of injury caused by balloon angioplasty is associated with acute closure and restenosis.In a new ex vivo whole artery angioplasty model, we examined the roles of thrombin inhibition with D-Phe-Pro-ArgCH2Cl (PPACK) and inhibition of the platelet membrane fibrinogen receptor glycoprotein IIb/IIIa (GPIIb/IIIa) with monoclonal antibody 7E3 on platelet deposition at the site of balloon injury. Fresh rabbit aortas were mounted in a perfusion chamber. One half of the mounted arterial segment was dilated with a standard angioplasty balloon catheter and the uninjured half served as the control segment. The vessels were perfused with human blood at physiological pressure and shear rates of 180-250 second-1 for 30 minutes. Platelet deposition was measured using 111In-labeled platelets and scanning electron microscopy. With heparin (2 units/ml) anticoagulation, 8.2 +/- 2.2 x 10(6) platelets/cm2 were deposited at the site of balloon injury compared with 0.7 +/- 0.2 x 10(6) platelets/cm2 on uninjured segments (p less than 0.02, n = 7). PPACK was tested at a concentration (10 microM) that totally inhibited platelet aggregation in response to thrombin. 7E3 was tested at a concentration (10 micrograms/ml) that totally inhibited platelet aggregation. Platelet deposition at the site of balloon injury was reduced 47% by PPACK and 70% by 7E3 compared with heparin.At shear rates seen in nonstenotic coronary arteries, PPACK and 7E3 are more effective than heparin in reducing platelet deposition at the site of balloon injury. The significant inhibition of platelet deposition by PPACK demonstrates the importance of heparin-resistant thrombin in platelet thrombus formation. The 7E3 results suggest that approximately 70% of platelet deposition at the site of balloon injury is GPIIb/IIIa dependent and that the remaining 30% results from non-GPIIb/IIIa-mediated platelet-subendothelial adhesion. Finally, the ex vivo whole artery system is a useful model for studying platelet-vessel wall interactions under physiologically defined parameters.

Abstract

Thyroid disease, especially hypothyroidism, is common in patients with Hodgkin's disease who have been treated with irradiation. We reviewed the records of 1787 patients (740 women and 1047 men) with Hodgkin's disease who were treated with radiation therapy alone (810 patients), radiation and chemotherapy (920 patients), or chemotherapy alone (57 patients) at Stanford University between 1961 and 1989. Among these patients, 1533 were alive at the last follow-up, and 254 had died of causes other than Hodgkin's disease. (Four other patients were excluded from the analysis because they had undergone thyroidectomy before treatment for Hodgkin's disease. The thyroid was irradiated in 1677 patients. Follow-up averaged 9.9 years.A total of 573 patients had clinical or biochemical evidence of thyroid disease. Among the 1677 patients whose thyroid was irradiated, the actuarial risk of thyroid disease 20 years after treatment was 52 percent, and it was 67 percent at 26 years. Hypothyroidism was found in 513 patients. A total of 486 patients received thyroxine therapy for elevated serum thyrotropin concentrations and either low free thyroxine (208 patients) or normal free thyroxine values (278 patients); 27 had transient elevations of the serum thyrotropin level that were not treated. Graves' hyperthyroidism developed in 30 patients (2 of whom had not undergone thyroid irradiation), and ophthalmopathy developed in 17 of these patients. Ophthalmopathy developed in four other patients with Graves' disease during a period of hypothyroidism (n = 3) or euthyroidism (n = 1). The risk of Graves' disease was 7.2 to 20.4 times that for normal subjects. Silent thyroiditis with thyrotoxicosis developed in six patients. Forty-four patients were found to have single or multiple thyroid nodules, 26 of whom underwent thyroidectomy. Six of the 44 had papillary or follicular cancers. Among the patients who did not undergo operation, 12 had small functioning nodules, 4 had cysts, and 2 had multinodular goiters. The actuarial risk of thyroid cancer was 1.7 percent. The risk of thyroid cancer was 15.6 times the expected risk.High risks of thyroid disease persist more than 25 years after patients have received radiation therapy for Hodgkin's disease, reinforcing the need for continued clinical and biochemical evaluation. Prolonged follow-up confirms an elevated risk of thyroid cancer and Graves' disease as well as hypothyroidism in these patients.

Abstract

Since 1981, intraoperative bone scanning has been used at Stanford University Hospital to assist in the localization and excision of skeletal lesions in the surgical suite. The utility of bone scans to detect lesions not otherwise "visible" is valuable in guiding the surgeon to the pathological site. In addition, intraoperative scanning can define the exact amount of tissue to be excised, averting excessive surgery near joints or along weight-bearing bones. Seventeen cases are presented.

Abstract

Graves' disease is an organ-specific autoimmune disorder. There is no universal agreement on the mechanism of Graves' disease, but the over-activity of the thyroid is due to an antibody capable of attaching to and activating the TSH receptor of follicular cells. There are other extrathyroidal features that are not caused either by this antibody or by hyperthyroidism. The clinical diagnosis is generally straightforward and can be confirmed by in vitro measurement of thyroid hormones and TSH. A measurement of radioiodine uptake is also valuable. Treatment is not specific for the immunologic defect, but its purpose is to lower the thyroid hormone levels to normal. This can be achieved with antithyroid medication, radioiodine iodine-131, or thyroidectomy. In most clinical situations, a strong argument can be made for iodine-131 therapy, which is safe and definitive, although posttreatment hypothyroidism and the need for lifelong thyroxine are to be expected.

Abstract

Between April 1968 and February 1988, 311 patients with symptomatic and progressive Graves' ophthalmopathy were treated with megavoltage orbital radiotherapy. The patients were divided into three groups: I (156 patients) treated with 20 Gy/2 weeks; II (69 patients) treated with 30 Gy/3 weeks, and III (a most recent set of 86 patients) received 20 Gy/2 weeks. The degree of eye involvement was evaluated numerically before and after therapy for each of five parameters: soft tissue signs, proptosis, eye muscle impairment, corneal involvement, and sight loss. Pre-treatment and current thyroid diagnosis and status were also noted. To evaluate the effects of radiotherapy alone, follow-up was terminated at the time any eye surgery was done; for those not treated surgically the minimum follow-up was 12 months. Because there were significant demographic differences between the patient groups, the results of each group were analyzed separately. A stepwise linear regression analysis was performed to determine if there were any significant variables affecting outcome. Based on these data formulae were derived which enable outcome to be predicted in any patient. Before therapy more than 90% of patients in all groups had soft tissue and eye muscle involvement, whereas 65-75% had proptosis and about half 50% had some degree of sight loss. Radiotherapy arrested progression of ophthalmic parameters in all but 1-6% of the patients. Objective and symptomatic improvement was noted for all parameters assessed, but there was marked individual variability. The best responses were noted for soft tissue, corneal involvement, and sight loss; however over half the patients had some improvement in eye muscle function and proptosis. Factors which resulted in less favorable outcome included male gender, advanced age, need for concurrent therapy for hyperthyroidism, and no history of hyperthyroidism. No complications have been observed. No significant differences in outcome were observed between the two dosage schedules. Following radiotherapy 29% of patients subsequently underwent some form of eye surgery, mostly eye muscle surgery to correct diplopia. After radiotherapy corticosteroid therapy was stopped without relapse in 76%. Orbital radiotherapy can result in improvement in signs and symptoms of Graves' ophthalmopathy in the majority of patients. For the remainder of patients the disease manifestations can be stabilized to allow functional surgical correction.

Abstract

The Scientific Board of the California Medical Association presents the following inventory of items of progress in nuclear medicine. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, research workers, or scholars to stay abreast of these items of progress in nuclear medicine that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another.The items of progress listed below were selected by the Advisory Panel to the Section on Nuclear Medicine of the California Medical Association, and the summaries were prepared under its direction.

Abstract

To further clarify the role of leukocytes in the pathogenesis of ARDS, we studied the localization and kinetics of leukocyte migration using 111In-labeled autologous white cell scans (111In wbc scans) in four primates made acutely septic with infusions of Escherichia coli. Whole body images were obtained with a gamma camera and were acquired on computer every 15 min beginning immediately after the E. coli infusion. Simultaneous measurements of C5a and peripheral blood leukocyte count were also obtained. Within 5 min of initiating sepsis, three major events occurred: complement activation as measured by the production of C5a, a profound fall in peripheral leukocyte count, and a significant increase in the sequestration of leukocytes in the lungs. The pulmonary sequestration reached a peak at 15 min with a mean of 152% of baseline activity. This sequestration consisted of a population that was predominantly neutrophils. Damage to the pulmonary capillary endothelium was demonstrated by an increase in extravascular lung water. The results support a role for neutrophils and complement as mediators in the pathogenesis of ARDS.

Abstract

The individual roles of pulmonary capillary endothelial and alveolar epithelial permeability in the pathogenesis of the adult respiratory distress syndrome (ARDS) are unclear. We developed a method for the sequential assessment of pulmonary macromolecule accumulation and small solute clearance in vivo using a gamma camera. We measured the exponential clearance coefficient of 111In-labeled diethylene triamine penta-acetate (111In-DTPA) to assess airway clearance of small solutes. We also calculated the exponential equilibration coefficient of 111In-labeled transferrin (111In-TF) to assess intrapulmonary accumulation of transferrin. We determined these parameters in guinea pigs with Escherichia coli peritonitis and compared them with a saline-treated control group, oleic-acid-treated groups, and a group treated with low molecular weight dextran Ringer solution. The pulmonary DTPA clearance and the intrapulmonary transferrin accumulation were significantly increased in the peritonitis group (29.4 +/- 8.2 x 10(-3) min-1, p less than 0.02, and 15.1 +/- 3.1 x 10(-3) min-1, p less than 0.02) when compared with the control group (3.1 +/- 0.8 x 10(-3) min-1 and 4.5 +/- 0.5 x 10(-3) min-1). These changes developed within 5.5 h of the initial insult. Neither increased extravascular lung water nor elevated pulmonary artery and left atrial pressures were detected in the peritonitis group. The low molecular weight dextran Ringer group did not show a significant increase in the pulmonary DTPA clearance and the intrapulmonary transferrin accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract

Scintigraphic techniques play an important role in the diagnosis and evaluation of a wide variety of musculoskeletal injuries. They provide physiologic and pathophysiologic information but do not provide the exquisite resolution of computed tomography or magnetic resonance imaging. Thus, scintigraphy studies should be ordered only when they would be expected to provide data that will establish a diagnosis or help in planning therapy.

Abstract

A 42-yr-old woman had a solitary metastases to her spine (T2) from a malignant struma ovarii. The thyroid was excluded as the site of the primary cancer. The lesion caused paraparesis. The spinal metastasis was treated by surgery and two doses of 131I (200 mCi each time). The patient responded very well and is entirely free of symptoms and signs. Repeat whole-body 131I scan shows no abnormality.

Abstract

Over the last decade, the role of nuclear medicine studies in the diagnosis of acute osteomyelitis has been discussed in depth in the literature. Yet, the respective roles played in this setting by each of the commonly used radionuclide studies often are confusing. In an attempt to develop a cogent diagnostic strategy, we reviewed the literature published within the last 12 years pertaining to the use of radiophosphate bone scintigraphy as well as gallium and indium WBC imaging in the diagnosis of this condition. Based on our findings, we propose an alternative approach to the evaluation of a patient with suspected acute osteomyelitis.

Abstract

The role of nuclear medicine studies in diagnosing late complications of fractures is described. Static bone scintigraphy is not helpful in predicting delayed or non-union of fractures. Several investigators have developed simple formulae comparing uptake in fracture site with adjacent or contralateral normal bone and described criteria that will predict problems with healing. These types of tests should only be used in patients who are at risk for delayed union. The scintigraphic diagnosis of infection complicating a fracture is difficult. Bone scintigraphy alone is not useful and combined 67Ga/99mTc MDP scanning has been disappointing. Most published series support the role in 111In WBC in this situation, but not all cases are correctly diagnosed. 111In (Chloride) cannot differentiate an infected from a delayed-healing fracture. Bone scintigraphy has a significant role in determining whether a bone graft is viable or not. Reflex sympathetic dystrophy is a rare complication of a fracture; it can be diagnosed by increased periarticular uptake on bone scan in all the joints of the affected part. Bone scintigraphy, especially when done with SPECT, is a very sensitive test for the diagnosis of avascular necrosis (AVN).

Abstract

Serum thyrotropin (TSH) concentrations were measured serially in 14 heart-transplant recipients (group 1) and 21 patients undergoing coronary artery bypass surgery (group 2), all without thyroid disease, and randomly in 158 patients hospitalized for various other nonthyroidal illnesses, including 144 judged euthyroid (group 3), six with increased FT4 and (or) T3 (group 4), and eight classified hypothyroid by conventional tests. The serial measurements indicated profound fluctuations. In group 1, TSH was subnormal in 21% of studies and increased in 10%. In group 2, corresponding abnormalities were found in 7% and 13%, respectively. Transiently low or high TSH tended to be associated with normal free thyroxin (FT4), prolonged subnormal TSH (greater than 1 week) with subnormal FT4. By contrast, subnormal TSH plus elevated FT4, or high TSH plus low FT4, were not encountered, making it unlikely that they occur by chance in severely ill patients who are not also hyper- or hypothyroid. In group 3, a suppressed TSH (plus borderline high FT4, T3/FT3) identified four cases of subclinical hyperthyroidism; however, another 11% of patients had subnormal and 10% had above-normal TSH, paired with normal FT4 and no evidence of thyroid disease. In group 4, suppressed TSH confirmed hyperthyroidism in five of six patients, and all in group 5 had increased TSH. We conclude that, in the hospital setting, sensitive TSH measurement can help to detect or confirm mild hyperthyroidism, but the positive predictive value of TSH alone may be as low as 35%.

Abstract

Twenty-two potential cardiac allograft donors had evaluation of thyroid function performed just prior to cardiectomy. Despite statistically significant abnormal thyroid function, no correlation to graft function or failure was observable. Multiple myocardial microinfarcts, undetected at the time of donor selection were detected in two hearts that were abandoned prior to transplantation and possibly another heart that failed as an allograft in a heart-lung transplant recipient.

Abstract

A survey of 67 nuclear medicine departments revealed no agreement on which radiolabeled agents could be injected through intravenous lines (IVs) and which required direct venipuncture. Labeled cells and several common radiopharmaceuticals were tested for adherence to intravenous tubing. Residual activity remaining in the tubing after an adequate flush was less than 1% of the injected dose in each case. Administration of radiolabeled agents through existing IVs is an acceptable alternative to direct venipuncture in many cases.

Abstract

One hundred sixty-two white-blood-cell scans were retrospectively reviewed to determine the sensitivity and specificity of the test for pulmonary and pleural infection. All scans were performed 18-24 hr after injection of indium-111 oxine-labeled autologous or donor cells. Pulmonary activity was graded on a scale of 0-4: 0 = equal to soft tissue; 1 = greater than soft tissue but less than rib; 2 = equal or greater than rib but less than liver; 3 = equal or greater than liver but less than spleen; 4 = equal to spleen. Activity was also characterized as being focal or diffuse. The white-blood-cell scan findings were correlated with the clinical diagnosis on the basis of physical examination, laboratory results, chest radiographs, clinical course, and pathologic studies when available. As pulmonary activity increased from grade 1 to 4, sensitivity declined from 93% to 14% and specificity increased from 64% to 100%. The sensitivity and specificity of focal uptake were 31% and 89% vs 62% and 74% for diffuse pulmonary activity. Making a distinction between focal and diffuse activity did not improve the specificity of low grades of pulmonary activity. The white-blood-cell scan can be very sensitive or very specific for pulmonary or pleural infection, depending on the criteria selected for a positive scan.

Abstract

The lack of a rapid, noninvasive, and accurate method to confirm or rule out prosthetic graft infection continues to constitute a compelling and vexing clinical problem. A host of adjunctive diagnostic techniques has been used in the past, but early promising results subsequently have usually not yielded acceptable sensitivity (reflecting false negatives) and specificity (reflecting false positive) data. White blood cell (WBC) indium 111 scanning has recently been added to this list. The utility and accuracy of 111In WBC scans were assessed by retrospective review of WBC scan results in 70 patients undergoing evaluation for possible prosthetic graft infection over a 7-year period. Operative and autopsy data (mean follow-up, 18 months for survivors with negative scans) were used to confirm the 22 positive, 45 negative, and three equivocal WBC scans. The false positive rate (+/- 70% confidence limits) was 36% +/- 6% (n = 8) among the 22 patients with positive scans (44% +/- 6% [11 of 25] if the three equivocal scans are included as false positive), yielding a specificity of 85% +/- 5% and an overall accuracy rate of 88% +/- 4% (80% +/- 5% and 84% +/- 5%, respectively, if the three equivocal cases are considered as false positive). All three patients with equivocal scans ultimately were judged not to have prosthetic graft infection. As implied by the high accuracy rate, the sensitivity of the test was absolute (100% [14 of 14]); there were no false negative results. (ABSTRACT TRUNCATED AT 250 WORDS)

Abstract

Thirty-two patients with orbital pseudotumor (18), reactive lymphoid hyperplasia (2), atypical lymphoid infiltrate (4) or malignant lymphoma (8) were treated in the Division of Radiation Therapy at Stanford University between January 1973 and May 1983. Of the 20 patients with pseudotumor or reactive lymphoid hyperplasia, 10 had unilateral lesions and 10 had bilateral lesions. Biopsy samples were obtained in 15 patients; in five patients with bilateral disease the diagnosis was made on the basis of computed tomography (CT) and clinical findings. The majority of patients were referred because of disease refractory to treatment with corticosteroids. The patients were given a mean dose of 2360 rad using complex, individualized megavoltage techniques including lens shielding. Radiotherapy was well tolerated with no significant acute or late complications. Fifteen patients had complete resolution of symptoms after treatment; five had continued symptoms. Of the 12 patients with malignant lymphoma or atypical lymphoid infiltrate, four had systemic lymphoma with orbital involvement and eight had orbital involvement only. The diagnosis was made by biopsy in all patients and immunophenotyping was done in six cases, of which 5 were monoclonal. Patients were evaluated with a chest radiograph, lymphogram or abdominal CT, bone marrow biopsy and orbital CT. A mean dose of 3625 rad was delivered to the orbit only. Most of the patients received complex megavoltage treatment using bolus. All patients in this group had a complete response and local control. There were no relapses in those with localized disease. Two patients developed cataracts. Carefully planned orbital radiotherapy provides local control without symptomatic sequelae for orbital masses ranging from pseudotumor to malignant lymphoma.

Abstract

A two-site immunoradiometric assay for serum thyrotropin (TSH) was modified to improve the analytical sensitivity. The sensitivity achieved (detection limit, approximately 0.1 microU/ml; lower limit of quantitative measurement, approximately 0.4 microU/ml) was comparable to that of the best competitive binding research assays, yet this assay can be performed routinely. Serum TSH was 1.82 +/- 0.69 (mean +/- s.d.) (range 0.4-3.4 microU/ml) in healthy individuals and 1.83 +/- 0.90 microU/ml (range 0.7-3.7 microU/ml) in patients with nonthyroidal disorders. By contrast, 97% of clinically hyperthyroid patients (Graves' disease, toxic nodular goiter) with high serum free T4 (FT4) and T3 had suppressed serum TSH values, i.e., less than 0.3 microU/ml. Among patients with euthyroid Graves' ophthalmopathy or nontoxic goiter those clinically suspected of mild hyperthyroidism had TSH values less than 0.3 microU/ml, while those judged euthyroid had normal values. A large proportion of thyroid patients on antithyroid drugs (poorly to well-controlled) had suppressed TSH. Of Graves' patients in remission (normal FT4 and T3), 75% had normal TSH, but individual levels changed significantly over time, suggesting that a progressive decline in TSH may be useful in predicting recurrences. In hypothyroid patients taking L-T4, serum TSH was subnormal in patients with elevated FT4, but TSH was also low in six patients clinically suspected to be thyrotoxic despite normal FT4 and T3 and in 32% of asymptomatic patients with normal thyroid hormone levels. Conversely, 23% of thyroid cancer patients who had undergone thyroidectomy were taking insufficient L-T4 to completely suppress TSH secretion. In 25 individuals who underwent thyrotropin releasing hormone (TRH) stimulation tests, the baseline serum TSH value correlated well with the peak serum TSH value post-TRH (r = 0.85). We conclude that sensitive TSH measurements could establish or confirm the diagnosis of hyperthyroidism in equivocal cases, replace most TRH-stimulation tests and be of value in optimizing L-T4 suppression therapy for thyroid cancer patients post-thyroidectomy.

Abstract

Thyroid function was measured in 119 children, 16 years of age or less, after radiotherapy (XRT) for Hodgkin's disease. Thyroid abnormalities developed in 4 of 24 children (17%) who received 2600 rad or less, and in 74 of 95 children (78%) who received greater than 2600 rad to the cervical area, including the thyroid. The abnormality in all but three (one with hyperthyroidism and two with thyroid nodules) included the development of elevated levels of thyroid stimulating hormone (TSH). Age, sex, and administration of chemotherapy were not significant factors in the development of thyroid dysfunction. All children had lymphangiograms (LAG) and no time relationship was noted between thyroid dysfunction and LAG-XRT interval. The mean interval from radiotherapy to documented thyroid dysfunction was 18 months in the low-dose group and 31 months in the high-dose group, with most patients becoming abnormal within 3 to 5 years. Of interest was a spontaneous return of TSH to within normal limits in 20 children and substantial improvement in another 7. This study confirms the occurrence of dose-related occult hypothyroidism in children following external irradiation of the neck.

Abstract

We compared two commercial assays for measurement of serum thyroglobulin [Nuclear Medical Systems (NMS) and "CIS" (Damon Diagnostics)] with each other and with one developed at Stanford (J Clin Endocrinol Metab 49:557-564, 1979). The NMS assay is a competitive-binding RIA, the CIS and Stanford assays are two-site immunoradiometric assays. The kit standards varied in thyroglobulin concentration. The NMS standards differed in immunoreactivity from thyroglobulin in clinical specimens and from the other standards. Also, nonparallelism between standards and patients' sera in the NMS assay suggested a less-specific antiserum. Results by the CIS and Stanford assays correlated well (n = 120, r = 0.964), those by the NMS assay less strongly (n = 101, r = 0.855 vs CIS, r = 0.888 vs Stanford). Clinical evaluation in 50 patients treated for differentiated thyroid carcinoma (10 with metastases and 40 currently disease-free) indicated good agreement for positive results by the three assays. The CIS and the Stanford assay both gave high results (greater than or equal to 25 micrograms/L) in all 10 cases with metastases; the NMS RIA identified eight of these patients (thyroglobulin greater than or equal to 30 micrograms/L), but excluded two with anti-thyroglobulin autoantibodies. In subjects without disease, however, the percentage of undetectable thyroglobulin (negative result), as opposed to low measurable thyroglobulin (inconclusive result) varied considerably: 85% by CIS, 30% by NMS, and 75% by the Stanford assay.

Abstract

Early and accurate diagnosis of infected prosthetic arterial grafts is difficult, despite the application of diverse diagnostic modalities. Delay in making the diagnosis is largely responsible for the high amputation and mortality rates associated with this complication. In nine patients with suspected graft infections, indium-111 white blood cell scanning was useful and accurate. Graft infection was proved in five cases and ruled out in three. One false-positive scan was due to a sigmoid diverticular abscess overlying the graft. Indium-111 white blood cell scans may improve the accuracy of diagnosing infected prosthetic grafts, which may result in better limb and patient salvage rates.

Abstract

Rest myocardial 201T1 scintigraphy was undertaken in 15 males mean age 39 years (22-54) who had been accepted for cardiac transplantation. Complete pathological correlation was obtained in 14 after transplantation and in 1 who died before a suitable donor heart became available. The average time from scintigraphy to pathological evaluation was 42 days (9-103). All the 201T1 images were grossly abnormal and on the basis of these studies it was not possible to differentiate ischemic from idiopathic cardiomyopathy. Each of the three views of the 201T1 study was divided into three segments, therefore 135 areas were available for comparison (3 x 3 x 15). Eighty-eight of these were abnormal on scan and 78 of these were abnormal pathologically. The right ventricle was seen on all rest images but the degree of uptake bore no relationship to the measured thickness of the right ventricular wall. Structures such as the atrial wall and the enlarged papillary muscle were visualized in some patients. In two patients there was an improvement of the rest 201T1 image in delayed views and histologically these areas showed a mixture of muscle and fibrous tissue. The sensitivity of 201T1 imaging in this study was 89% and there was close correlation of the images with gross and microscopic pathological findings.

Abstract

We previously reported a patients who developed fulminant pneumococcal sepsis 12 years after successful treatment for Hodgkin's disease, which included splenic irradiation. We have since evaluated splenic size and function in 25 patients who had received splenic irradiation 5 to 16 years previously either for Hodgkin's disease (n = 19) or non-Hodgkin's lymphoma (n = 6). Mean maximum splenic diameter as measured on a 99mTc-sulfur colloid liver-spleen scan was 6.2 cm in the irradiated group and 9.7 cm in a control group (p less than 0.001). The mean percentage of erythrocytes containing pits when observed with interference phase microscopy was 13.0% in the irradiated group, which was significantly different (p less than 0.001) from the levels found in each of the control groups: normal subjects, 0.9%; unstaged and untreated lymphoma patients, 0.6%; and patients after splenectomy, 33.7%. Patients who have had splenic irradiation should be considered at risk of developing overwhelming pneumococcal sepsis.

Abstract

Lymphocytes separated from venous blood from six dogs who had heterotopic cardiac transplants have been labeled using 111In-oxine. Labeled lymphocytes were reinjected into the dogs and imaging of the heart carried out over the successive 3 or 4 days. For comparison serial ECGs and punch biopsies of the heart were obtained. Abnormal uptake of labeled lymphocytes in the donor heart was clearly visible in three of the six dogs, faintly visible in two and not seen in one. 630 mu Ci 111In was used in the dog where no uptake was seen and subsequent studies showed this amount of the radiopharmaceutical was toxic to lymphocytes. In the remaining five dogs the mean ratio of uptake of 111I in donor to recipient heart was 14:1 (range 6.5:1--21:1). The lack of substantial uptake in the transplanted heart of two dogs in attributed to a delay in rejection relative to the time the labeled lymphocytes were injected. The results suggest that 111In-labeled lymphocytes have potential as a noninvasive test for detecting rejection of cardiac transplants.

Abstract

During severe systemic illness total thyroid hormone levels are often low, and measurement of total hormones often does not differentiate between euthyroid and hypothyroid patients. Therefore, we examined serum free thyroxine levels by radioimmunoassay (antibody-coated tubes, Clinical Assays) as an alternative diagnostic test in three groups of severely ill patients with subnormal triiodothyronine. Free thyroxine estimates agreed with the clinical impression and TSH in 91% of cases in group 1 (47 patients with no history or clinical evidence of thyroid disorder), in 96% of cases in group 2 (24 euthyroid patients with a previous history of thyroid disease, including some on thyroid replacement) and 90% of cases in group 3 (10 hypothyroid patients). By contrast, the free thyroxine index did so in only 53% (group 1), 46% (group 2) or 100% (group 3). Sequential studies showed little change in free thyroxine and TSH levels in euthyroid patients during illness and recovery, and a good negative correlation between free thyroxine and TSH in hypothyroid patients. Free thyroxine measurements (and TSH) discriminate between euthyroid and hypothyroid sick patients better than other thyroid function tests including the free thyroxine index, and can be employed routinely: a distinct advantage over free thyroxine measured by equilibrium dialysis.

Abstract

Free thyroxine concentrations were determined by radioimmunoassay in 96 infants within an intensive care nursery and in 32 healthy term infants. Sera for free T4 levels were drawn simultaneously with the filter paper specimens for T4 obtained to screen these infants for congenital hypothyroidism. The mean free T4 level in 20 adults was 1.38 +/- 0.03 ng/dl (mean +/- SEM). The mean in the ICN infants was 3.48 +/- 0.18 ng/dl and in healthy term infants, 4.24 +/- 0.23 ng/dl. Like T4, free T4 correlated positively with increasing gestational age and birth weight, and was lower in infants with RDS. Although 66% of the ICN infants had T4 levels below the statistically selected screening level (fifth percentile), all of these infants had free T4 levels greater than 0.8 ng/dl. Two additional infants with untreated congenital hypothyroidism has free T4 levels of 0.3 and 0.4 ng/dl. The measurement of free T4 appears to be an accurate indicator of thyroid function in these infants.

Abstract

Free thyroxine (FT4) has been measured in two groups of patients, before and after heparin, using equilibrium dialysis (ED) and two radioimmunoassays, RIA-I and RIA-II. In Group A, nine patients were tested before and after 12-24 hr of intravenous heparin, FT4 (ED) rose from 1.9 +/- 0.5 to 2.8 +/- 3.0 ng/dl, and RIA-I from 1.37 +/- 0.37 to 1.89 +/- 1.21 ng/dl, whereas RIA-II results fell from 0.97 +/- 0.38 to 0.66 +/- 0.32 ng/dl. In Group B, ten patients were tested before and after 15 min of intravenous heparin. FT4 (ED) rose from 1.7 +/- 0.7 to 3.2 +/- 1.6 ng/dl (p less than 0.02), and RIA-I rose from 1.3 +/- 0.46 to 2.02 +/- 0.01 ng/dl (P less than 0.05), whereas RIA-II results fell from 1.07 +/- 0.38 to 0.63 +/- 0.31 ng/dl (P less than 0.02). The correlation coefficient between FT4 (ED) and RIA-I in 38 paired results was 0.96, but there was no correlation between FT4 (ED) and RIA-II results.

Abstract

The possibility of diagnosing transplant rejection using Tc-99m-PYP imaging was examined in 12 cardiac transplant recipients. Two patients were studied on two occasions. The presence or absence of active rejection was established by endomyocardial biopsy. The intensity and pattern of myocardial uptake of the tracer did not differ significantly in the two patients studied at the time of rejection compared to the remainder. It is concluded that a single Tc-99m-PYP study cannot be used to diagnose cardiac transplant rejection.

Abstract

Using the angiographic findings as the standard, we have examined the sensitivity and specificity of ECG-gated static thallium-201 myocardial images in 54 patients undergoing selective coronary arteriography. Gated and nongated images, each in anterior, 45 degrees LAO, and 65 degrees LAO projections, were processed by interpolative background subtraction. They were then analyzed separately by four independent observers who were unaware of patient identity, the results of coronary arteriography, and which studies were gated or nongated. No significant differences were observed between the gated and nongated images regarding sensitivity or specificity, the detection rate for reversible myocardial ischemia, the accuracy of prediction of arteriographic extent of disease, or the degree of inter- or intraobserver variability. We conclude that ECG-gated acquisition of T1-201 images does not produce any significant advantages, at least when interpolative background subtraction is used.

Abstract

Three patients (two female and one male), who had received mantle irradiation for Hodgkin's disease eight, ten, and twelve years previously, developed papillary thyroid carcinoma. The radiation doses to the necks overlying the site of thyroid cancers were 3000, 4000, and 4100 rads, respectively. It has been stated that there is no risk of developing thyroid cancer with such high doses of external irradiation but apparently this complication will be encountered in a small number of patients.

Abstract

Computed tomography (CT) is now the standard method of confirming a diagnosis of suspected subdural empyema. We report a case in which the radionuclide brain scan was abnormal at a time when the CT scan was normal. An Indium-111-labeled leukocyte scan was also performed in this patient and demonstrated abnormal uptake in the empyema. The scintigraphic findings in a second case of subdural empyema are also described. The relative roles of radionuclide studies and CT scans in the patient with suspected subdural empyema are discussed.

Abstract

Space-occupying lesions in the liver are usually seen as photon-deficient areas on 99mTc sulfur colloid liver scans, irrespective of the underlying disease. The results of combined 111In white blood cell scans and sulfur colloid scans in three patients in whom the clinical diagnosis was either cancer or abscess are described. In the first patient, the 111In scan showed increased uptake in a region of the liver where 99mTc sulfur colloid scan showed a negative defect. Abscess was diagnosed. In the other two patients, both 111In and 99mTc scans showed cold lesions and cancer was believed to be the most likely diagnosis. These diagnoses were confirmed by biopsy. It is suggested that simultaneous white blood cell scans and sulfur colloid imaging provide additional specificity in diagnosis of hepatic masses.

Abstract

An immunoradiometric assay for thyroglobulin (Tg), which allows quantification of Tg in the presence of anti- Tg, has been evaluated in patients with differentiated thyroid cancer. All patients had undergone thyroidectomy plus I- 131 ablation. Three separate studies have been conducted. 1. Tg levels were compared with I- 131 whole-body scans made at 48 hr in 22 patient studies. Both tests gave similar results in 19 of the studies, but in three patients the results of the tests were discordant. 2. Tg levels were compared with clinical status in 18 patients who were free of disease; 15 had Tg values < 5 ng/ml, and three had measurable but normal Tg values. Three patients with metastatic disease had measurable Tg, and in two the values were above normal. 3. Sequential Tg measurements were made at intervals of 3 mo in 19 patients on thyroxine. Fifteen of these patients had identical results on two or more occasions.

Abstract

We have evaluated a radioimmunoassay for free thyroxine (FT4) involving antibody-coated tubes (GammaCoat 125I Free T4RIA; Clinical Assays, Div. of Travenol Labs, Inc.). The coefficient of correlation between FT4 and the FT4 index was 0.98 for all patients with various thyroid disorders, 0.77 for hospitalized patients with miscellaneous diseases, and 0.74 for healthy individuals. FT4 values also agreed well with triiodothyronine or thyrotropin concentrations in these patients and were consistent with each patient's clinical status. Patients with severe nonthyroidal illnesses and abnormal thyroid-function tests, despite clinical euthyroidism, had normal FT4 values. In this group, the mean FT4 was almost identical to that in the controls, although mean thyroxine, triiodothyronine, and FT4 index differed significantly and the correlation between FT4 and FT4 index was poorer (r = 0.66). For most patients, the diagnostic value of FT4 measurements is comparable to that of the FT4 index, and it may be superior in patients with severe nonthyroidal illnesses. The test costs less and saves time as compared to the FT4 index computation, and it can be used routinely with thyrotropin assay for the diagnosis of hypothyroidism or with triiodothyronine assay for the diagnosis of hyperthyroidism.

Abstract

Indium-111 oxine, polymorphonuclear cells isolated and labeled with 111In were used for studying absecesses and inflammatory conditions. There were 64 total scans done in 59 patients, 32 male and 27 female, aged 3-81 years (average, 51). The original clinical diagnosis was abscess in 33 patients. The whole blood cell scan was abnormal in 12 (36%) of these, and a good clinical correlation was obtained in 11 of the 12. In the 21 with a normal scan, 18 had no evidence of abscess, yielding one false-positive and three false-negative interpretations in the abscess group. Thirteen patients had fever of unknown origin, nine had negative scans and no subsequent evidence of abscess, and four had positive scans with good correlation in three. Acute bone and joint infections were positive on scan (4/4), whereas chronic osteomyelitis was negative (0/2). Three patients with acute myocardial infarction and three of four with subacute bacterial endocarditis had normal scans. All three studies in renal transplant rejection showed positive uptake in the pelvic kidneys. Indium-111 white blood cell scans have proved useful to diagnose or exclude a diagnosis of abscess or inflammatory condition infiltrated with polymorphonuclear leukocytes.

Abstract

Seventeen of 265 bone scans in children receiving chemotherapy for various malignant diseases exhibited intense renal parenchymal uptake of radioactivity during bone imaging. In a retrospective analysis, it was learned that uptake occurred when imaging was performed within one week of cancer chemotherapy. It was encountered after injection of cyclophosphamide (P less than 0.05), vincristine (P less than 0.01), and doxorubicin (P less than 0.02). In this series, none of the 265 scans showed intense renal uptake unless the patient received chemotherapeutic drugs in the preceding week. This finding did not seem to result from altered renal function, and the exact cause has not been defined.

Abstract

The in vivo distribution of vesicles containing radiopharmaceuticals in their cavities has been studied using three routes of administration: intravenous, subcutaneous, and intraperitoneal. The in vivo distribution in mice was determined by dissection of the animals and calculation of radioactivity in the organs. In rats the in vivo distribution was assessed by scintigraphy using a scintillation camera-digital computer unit. After intravenous injection of vesicles, radioactivity is concentrated to some extent in the liver and spleen but the pattern of distribution is different from that of the corresponding free radiopharmaceutical or radiocolloid made of the corresponding radionuclide. The permeability of the vesicular membrane to contained radiopharmaceutical has been shown to vary according to the chemical composition of the vesicles. Vesicles can be used to introduce materials in vivo and the potential exists for their specific targeting by coupling other molecules to their surfaces.

Abstract

Artificial spherules or vesicles of 900 A in diameter formed from phosphatidylcholine and gangliosides and enclosing 99mTcO4 - (standard preparation) survive intact in the circulation of the mouse. Polyamino acids and protein have been incorporated into and onto the vesicles; such vesicles remain intact as determined by diffusion dialysis studies and by electron paramagnetic resonance studies of vesicles enclosing spin label. In studying the distribution of polyamino acid-vesicles and protein vesicles in vivo, it was found that the latter distribute differently from standard vesicles or free protein alone whereas aromatic polyamino acid-vesicles concentrate in the liver and spleen to a greater extent than standard vesicles. We conclude that the permeability and stability characteristics of vesicles may be preserved when they are modified by the addition of protein or polyamino acids and that such modification of vesicles may be associated with an alteration of their fate in vivo. The potential exists to use vesicles as carriers of radiopharmaceuticals and other drugs and to direct the vesicles preferentially to tissue targets in vivo.

Abstract

The results of total skeletal scintigraphy with technetium 99m-labeled diphosphonate in 200 patients with biopsy-proven primary cancer demonstrated abnormalities in 114; 57 had normal roentgenograms. In 32 of the 57 patients, the abnormalities were ascribed to malignant lesions. This is a false-negative rate of 17% for the roentgenographic examinations. Only three patients had abnormal roentgenograms but normal scans, a yield of 1.6% false-negative scans. In a comparison of scan and roentgenographic findings with the skeleton divided into 12 regions, 119 of 160 abnormalities seen on scans but not on roentgenograms were attributed to tumor. Only five of 17 regions that were abnormal on roentgenogram but not on scans were unexplained false-negative findings. Thus, on a regional basis, the yields of false-negative roentgenograms and scans were 9.1% and 0.4%, respectively.

Distribution and fate of synthetic lipid vesicles in the mouse: a combined radionuclide and spin label study.Proceedings of the National Academy of Sciences of the United States of AmericaMcDougall, I. R., Dunnick, J. K., McNamee, M. G., KRISS, J. P.1974; 71 (9): 3487-3491

Abstract

Single compartmental spherules of various lipid constituents (vesicles), enclosing (99m)TcO(4) (-) as a radioactive marker, were injected intravenously into C(3)H mice, and the distribution of radioactivity was studied. About 25% of the administered radioactivity was present in the liver 5 min and 30 min after the injection of vesicles composed of phosphatidylcholine and gangliosides, which were sonicated for 5 min (standard preparation). About 10-20% of the radioactivity remained in the circulation. By use of a nonradioactive spin label (tempocholine) enclosed within vesicles, intact vesicles were demonstrated in the circulation for 46 min after intravenous injection. The distribution of radioactivity from (99m)TcO(4) (-) inside vesicles is very different from that of free (99m)TcO(4) (-) or of (99m)Tc sulfur colloid. Increase in the length of sonication or incorporation of cholesterol into the wall of the vesicles enhanced hepatic levels and reduced blood levels of radioactivity. These same manipulations also slowed the rate of transfer of (99m)TcO(4) (-) out of vesicles in dialysis experiments in vitro. Addition of phosphatidic acid, phosphatidylethanolamine, or phosphatidylserine to the standard constituents did not greatly alter the distribution of radioactivity in vivo but did increase the number and type of active coupling sites on the outside of the vesicle. The results indicate that vesicles might be valuable as carriers of diagnostic or therapeutic agents.